Epidemiological studies indicate that cofactors may be involved in the rate of progression of acquired immunodeficiency disease (AIDS) and certain mycoplasmas, especially Mycoplasma fermentans strain incognitus, have been proposed as cofactors. The mitogenic properties of mycoplasmas could increase HIV production by infected lymphocytes; other mitogens that act on T cells are known to enhance HIV production in vitro. Furthermore, increased virus production is known to be associated with clinical progression of disease in HIV-infected individuals. An animal model will be needed to prove whether or not cofactors are involved, and of the available models, simian immunodeficiency virus (SIV) in macaques is the most similar to HIV infection of humans. Our long term goals are to use the SIV model to determine (i) whether M. fermentans is a cofactor for SIV infection and accelerates development of AIDS-like disease; (ii) whether immunosuppression is required for M. fermentans infection; i.e., M. fermentans is only an opportunistic pathogen; and (iii) the mechanisms by which M. fermentans and SIV interact in either situation. Specific objectives for the current proposal are to: determine which strains of M. fermentans, including isolates from AIDS patients, nonspecifically activate macaque lymphocytes and monocytes and characterize the responding lymphocyte subpopulation(s); determine the effects of these strains of M. fermentans on production of SIV in vitro and correlate this with nonspecific activation; determine if the SIV model is confounded by the presence of M. fermentans or indigenous mycoplasmas; characterize the ability of M. fermentans to infect macaques; use macaques infected with M. fermentans to delineate the natural history of M. fermentans infections, identify the site(s) of organism localization, and optimize cultural and serological assays; determine the effects of M. fermentans infection on SIV infection in vivo and on rate of progression of SIV-induced AIDS-like disease and correlate rate of progression with nonspecific activation of lymphoid cells and virus production. Almost all of the techniques to be used in these studies are established in the laboratories of the PI, CO-PI, or Co-Investigators. The virus to be used in these studies, SIVsmmPBjl4-bcl1 is a biological clone; the sequence of the virus is known, thus primers for the SIV PCR can be easily prepared.